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目的研究紫杉醇诱导人MCF-7细胞周期阻断及凋亡的分子机制。方法用流式细胞仪分析紫杉醇对MCF-7细胞周期变化的影响,用自制的含9 984个已知基因和EST的高密度基因芯片检测MCF-7细胞在不同浓度紫杉醇作用下的基因表达变化。结果MCF-7细胞在100 nmol.L-1紫杉醇作用24 h,流式细胞仪结果显示77.8%细胞阻断在G2/M期和1.3%细胞发生凋亡;基因表达谱分析发现:在12.5 nmol.L-1(IC50)及100 nmol.L-1紫杉醇作用下,分别有27及77个基因差异表达。结论紫杉醇可诱导MCF-7细胞周期阻断在G2/M期并引起部分细胞凋亡,该作用与药物浓度有关。基因表达谱分析显示部分差异表达基因参与细胞微管及骨架结构、细胞周期调控、以及DNA损伤修复和凋亡过程。
Objective To investigate the molecular mechanism of paclitaxel-induced cell cycle arrest and apoptosis in human MCF-7 cells. Methods Flow cytometry was used to analyze the effect of paclitaxel on cell cycle changes of MCF-7 cells. The expression of MCF-7 cells under different concentrations of paclitaxel was detected by using a homemade high-density gene chip containing 9 984 known genes and ESTs. . RESULTS: MCF-7 cells were treated with 100 nmol.L-1 paclitaxel for 24 h. Flow cytometry results showed that 77.8% cell blockage occurred in G2/M phase and 1.3% of cells. Gene expression profiling was found at 12.5 nmol. There were 27 and 77 genes differentially expressed by .L-1 (IC50) and 100 nmol.L-1 paclitaxel, respectively. Conclusion Paclitaxel can induce cell cycle arrest of MCF-7 in G2/M phase and induce apoptosis of some cells, which is related to drug concentration. Gene expression profiling revealed that some of the differentially expressed genes are involved in the microtubule and skeletal structure, cell cycle regulation, and DNA damage repair and apoptosis.